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Literature summary for 2.1.1.233 extracted from

  • Palanichamy, K.; Kanji, S.; Gordon, N.; Thirumoorthy, K.; Jacob, J.R.; Litzenberg, K.T.; Patel, D.; Chakravarti, A.
    NNMT silencing activates tumor suppressor PP2A, inactivates oncogenic STKs, and inhibits tumor forming ability (2017), Clin. Cancer Res., 23, 2325-2334 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.1.1.233

Inhibitors

Inhibitors Comment Organism Structure
S-adenosyl-L-homocysteine product inhibition Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0018
-
 [phosphatase 2A protein]-leucine pH and temperature not specified in the publication Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine Homo sapiens
-
 S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9UIC8
-
-

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine
-
 Homo sapiens S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
-
 ?

Synonyms

Synonyms Comment Organism
LCMT1
-
 Homo sapiens
leucine carboxyl methyl transferase 1
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
S-adenosyl-L-methionine
-
 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
3
-
 pH and temperature not specified in the publication Homo sapiens S-adenosyl-L-homocysteine

General Information

General Information Comment Organism
malfunction increased expression of NNMT selectively affects LCMT1 resulting in lower PP2A activation. Decreased LCMT1 expression or SAH concentration decreases endogenous activated PP2A Homo sapiens
metabolism nicotinamide-N-methyltransferase (NNMT, EC 2.1.1.1) outcompetes leucine carboxyl methyl transferase 1 (LCMT1) for methyl transfer from principal methyl donor SAM in biological systems, because NNMT has a higher affinity for SAM as compared to LCMT1. Inhibiting NNMT increases the availability of methyl groups for LCMT1 to methylate protein phosphatase 2A (PP2A) resulting in the inhibition of oncogenic serine/threonine kinases (STKs, EC 2.7.11.). Even if there are methylated products in the system by LCMT1, which is a O-methylating enzyme, they can potentially be reversed to unmethylated form due to their reversible nature and availability of demethylases such as PME1. In contrast, N-methylating NNMT enzyme product MNA which is stable and acts as methylation sink further favoring methyl transfer by NNMT compared to LCMT1. The NNMT-PME1-LCMT1 signaling axis is one mechanism by which the activity of the MAPK/Akt pathways are maintained in cancer cells Homo sapiens
physiological function methylation of protein phosphatase 2A (PP2A) activates PP2A activity Homo sapiens